A. Caride

Endosulfan effects on pituitary hormone and both nitrosative and oxidative stress in pubertal male rats.

The present study was undertaken to investigate in pubertal male rats possible effects of endosulfan administered throughout lactation and gestation on: (a) pituitary gene expression of prolactin, luteinizing hormone (LH), growth hormone (GH) and thyroid stimulating hormone (TSH); (b) circulating levels of these hormones; and (c) expression of nitric oxide synthase 1 and 2 (NOS1 and NOS2), and heme oxygenase-1 (HO-1) at pituitary level. Endosulfan was administered orally at the doses of 0.61 mg/kg/day or 6.12 mg/kg/day, and possible toxic effects were studied in pubertal male pups (at postnatal day 30). Gene expression was evaluated by RT-PCR and plasma hormone levels by RIA. Exposure to both administered doses down-regulated LH, GH and TSH. Treatment with 0.61 mg endosulfan/kg/day decreased prolactin expression, although its plasmatic concentration was decreased by both administered doses. LH secretion was stimulated by both doses, whereas the highest dose increased GH levels and decreased plasma TSH concentration. Endosulfan up-regulated NOS1 and NOS2. We can conclude that in pubertal male rat, prenatal and lactational exposure to endosulfan modifies expression and release of prolactin, LH, GH and TSH, and pituitary NOS1 and NOS2 mRNA levels, suggesting that nitrosative stress can be implicated in the endocrine toxicity of endosulfan at pituitary level.

Cadmium effects on 24 h changes in glutamate, aspartate, glutamine, GABA and taurine content of rat striatum

This work evaluates the possible changes in 24 h variations of striatal aspartate, glutamate, glutamine, gamma-aminobutyric acid (GABA) and taurine content after oral cadmium treatment. Male rats were submitted to cadmium exposure at two doses (25 and 50 mg/L of cadmium chloride (CdCl(2))) in the drinking water for 30 days. Control rats received cadmium-free water. After the treatment, rats were killed at six different time intervals throughout a 24 h cycle. Differential effects of cadmium on 24 h amino acid fluctuations were observed. Metal exposure modified the daily pattern of the amino acids concentration found in control animals, except for GABA and taurine with the lowest dose used. Exposure to 25 mg/L of CdCl(2) decreased mean content of aspartate, as well as GABA concentration. These results suggest that cadmium exposure affects 24 h changes of the studied amino acids concentration in the striatum, and those changes may be related to alterations in striatal function.

Toxic effects of methoxychlor administered subcutaneously on the hypothalamic-pituitary-testicular axis in adult rats.

This study was undertaken to evaluate the effects of methoxychlor MTX at the hypothalamic-pituitary-testicular axis in adult male rats. This global objective comprises three major aims: (1) to analyze the possible differential MTX effects in norepinephrine and serotonin concentration an in serotoninergic metabolism in anterior, mediobasal and posterior hypothalamus and median eminence; (2) to evaluate effects induced by MTX exposure on gonadotropins and testosterone; 93 to elucidate whether the regulatory interactions in the hypothalamic-pituitary-testicular axis are modified by this pesticide. Animals were administered subcutaneously 25mg/kg/day of MTX for 1 month. MTX increased norepinephrine and serotonin content in anterior hypothalamus (P < or = 0.05), but decreased serotonin concentration in posterior hypothalamus (P < or = 0.05). MTX diminished serotonin turnover in anterior hypothalamus (P < or = 0.01) and decreased plasma LH (P < or = 0.001) and testosterone (P < or = 0.05) levels but those of FSH remained unmodified. We can conclude that MTX exposure: (1) could exert differential effects in norepinephrine and serotonin concentration an in serotoninergic metabolism in anterior, mediobasal and posterior hypothalamus and median eminence, being the anterior hypothalamus the most sensitive region to the pesticide; (2) could inhibit LH and testosterone secretion without changing FSH; (3) four potential pathways might be involved in MTX effects on testosterone secretion (changing LH secretion; modifying serotonin and norepinephrine at the hypothalamic level; alterating the direct neural pathway between brain and testes; and/or by a direct effect in testes).

Cadmium chloride exposure modifies amino acid daily pattern in the mediobasal hypothalamus in adult male rat.

The present study was conducted to investigate the possible effects of cadmium exposure on the daily pattern of aspartate, glutamate, glutamine, gamma‐aminobutyric acid (GABA) and taurine levels in the mediobasal hypothalamus of adult male rats. For this purpose, animals were treated with cadmium at two different exposure doses (25 and 50 mg l−1 of cadmium chloride, CdCl2) in the drinking water for 30 days. Control age‐matched rats received CdCl2‐free water. After the treatment, rats were killed at six different time intervals throughout a 24 h cycle. CdCl2 exposure modified the amino acid daily pattern, as it decreased aspartate, glutamate, GABA and taurine levels at 12:00 h with both exposure doses employed. In addition, the treatment with 25 mg l−1 of CdCl2 induced the appearance of minimal values at 16:00 h and maximal values between 04:00 and 08:00 h for glutamate, and a peak of glutamine content at 20:00 h. The heavy metal also decreased GABA medium levels around the clock in the mediobasal hypothalamus. However, CdCl2 did not alter the metabolic correlation between glutamate, aspartate, glutamine and GABA observed in control animals. These results suggest that CdCl2 induced several alterations in aspartate, glutamate, glutamine, GABA and taurine daily pattern in the mediobasal hypothalamus and those changes may be related to alterations in hypothalamic function. Copyright

Toxic effects of methoxychlor in rat striatum: modifications in several neurotransmitters

Neurotoxic effects of methoxychlor (MTX) are poorly understood at present. This study was undertaken to evaluate the possible effects of MTX in norepinephrine, dopamine and amino acid contents and serotonin turnover in rat striatum. For this purpose, adult male Sprague-Dawley rats were administered 25 mg/kg/day of MTX in sesame oil or vehicle only for 30 days. The neurotransmitters of interest were measured in the striatum by HPLC. MTX decreased norepinephrine and 5-hydroxyindole acetic acid (5-HIAA) content and serotonin turnover (measured as 5-HIAA/serotonin ratio), and increased glutamate and GABA concentrations. However, the content of serotonin, aspartate, glutamine and taurine was not modified by MTX exposure. These data suggest that MTX exposure inhibits norepinephrine synthesis and serotonin metabolism. The inhibitory effect on norepinephrine could be explained, at least in part, by the increase of both GABA and glutamate contents. Further studies are needed to understand the effects of MTX on serotonin. Also a disruptive effect of MTX on the metabolisms of glutamate, aspartate, glutamine and GABA emerges.ResumenLos efectos neurotóxicos del metoxicloro (MTX) no son bien conocidos. Este trabajo se Ilevó a cabo para evaluar los posibles efectos de este pesticida en el contenido de norepinefrina, dopamina y aminoácidos, así como en el metabolismo serotoninérgico en cuerpo estriado. Para ello, a ratas macho adultas de la cepa Sprague-Dawley se les administró 25 mg/kg/día de MTX durante 30 días. A los animales del grupo control se administró aceite de sésamo, ya que éste era el vehículo en el que se administró el MTX en los animales tratados. La concentración estriatal de los neurotransmisores estudiados se determinó mediante HPLC. El MTX disminuyó el contenido de norepinefrina y de ácido 5-hidroxiidolacético (5-HIAA) y la tasa metabólica de serotonina (medida como la ratio 5-HIAA/serotonina), y aumentó las concentraciones de glutamato y GABA. Sin embargo, el contenido de serotonina, aspartato, glutamina y taurina no se modificó tras la exposición a MTX. Estos datos sugieren que la exposición a MTX inhibe la síntesis de norepinefrina y el metabolismo de serotonina. El efecto inhibitorio sobre la norepinefrina podría ser explicado, al menos en parte, por el incremento tanto del contenido de GABA como de glutamato. No obstante, se necesitan más estudios para entender los efectos del MTX sobre la serotonina. También se observa un efecto disruptor del MTX sobre el metabolismo del glutamato, aspartato, glutamina y GABA.